PDF(Pubmed)
Abstract：
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knock-out on the development of intestinal polyps using collaborative cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knock-out mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knock-out males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knock-out, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-nearest neighbors and linear regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides new information on understanding the intricate genetic interplay in the context of Smad4 knock-out, offering valuable insights that could inform the identification of potential therapeutic targets for juvenile polyposis and related diseases.
摘要：
青少年息肉病综合征（JPS）是一种罕见的常染色体显性疾病，其特征是胃肠道中的多个青少年息肉，通常与Smad4和BMPR1A等基因突变相关。这项研究探讨了Smad4敲除对使用协作交叉（CC）小鼠肠息肉发展的影响，基因多样化的模型。我们的结果表明，Smad4敲除小鼠在整个人群中肠息肉的显着增加，强调Smad4对息肉病的广泛影响。性别特异性分析表明，与WT同行相比，敲除男性和女性的息肉计数更高，具有不同的相关模式。线特定的效果突出了对Smad4淘汰赛的细微反应，强调遗传变异的重要性。多浊度热图提供了对息肉计数之间复杂关系的见解，地点,和尺寸。遗传力分析揭示了息肉数量和大小的重要遗传基础，而机器学习模型，包括k近邻和线性回归，确定关键预测因子，增强我们对青少年息肉病遗传学的理解。总的来说,这项研究为理解Smad4敲除的背景下复杂的遗传相互作用提供了新的信息，提供有价值的见解，可以为确定青少年息肉病和相关疾病的潜在治疗靶标提供信息。
